ORAL HEPARIN: New Route for Old Drug?

As the owner of two dogs, two cats, and a horse Dr. Mala Sivasankar can empathize with her clients' ordeals in giving medications to their pets: "To me, as a pet owner, it would be helpful to have easier ways of managing health problems in our animals."Nearly three years ago, the veterinary internal medicine resident at WCVM got her chance to do just that when she began a pilot project to investigate an easier way of administering one particular drug: heparin.

Known for its anticoagulant and antithrombotic effects, human physicians and veterinarians regularly use injectable forms of the drug - unfractionated or low molecular weight heparin to treat and prevent thromboembolism. Heparin
can also be given orally, but until a few years ago, scientists claimed that oral administration of the drug was ineffective because of poor absorption.

But thanks to the work of Dr. Linda Hiebert at WCVM, the medical profession has new respect for oral heparin. Using rat models, Hiebert discovered that oral heparin rapidly enters the body's circulation with much of the drug being taken up by the endothelium (layer of flattened cells that line blood vessels and some internal body cavities). She also showed that oral heparin effectively reduced the formation of blood clots with minimal alterations in coagulation parameters.

In veterinary medicine, the option of prescribing oral heparin could simplify long-term therapy for feline heart disease, Cushing's disease in dogs, and canine immune-mediated hemolytic anemia (IMHA) - conditions where blood clot development is a potential risk. "I think that the use of oral heparin would be of interest to owners of pets that may benefit from long-term heparin therapy," says Sivasankar, who worked on the study with Hiebert and her residency supervisor, Dr. Anthony Carr.

For example, veterinarians currently give subcutaneous injections of heparin to IMHA-affected dogs while they're hospitalized. But once
a dog is discharged, it may not be feasible for its owner to continue administering the heparin. An oral formulation would simplify the dosing process and allow heparin therapy to continue without frequent injections.

Sivasankar conducted the two-phase study during the summer of 2003. In the first stage, the resident gave the project's six dogs a single dose of oral heparin then collected samples of blood, urine and feces at intervals over 72 hours. In the second phase, Sivasankar gave the dogs a total of three doses (one dose every 48 hours) with samples collected over 120 hours.

Throughout the entire study, none of the dogs showed any clinical signs of bleeding (a potential side effect of heparin) nor did the drug cause any negative effect on the animals' coagulation parameters. However, unlike Hiebert's research with rat models, the pilot project didn't evaluate the dogs' blood vessels for evidence of heparin absorption or formation of clots. .Although the small number of dogs used in the study may have been a limiting factor, there were some promising trends seen in preliminary data.

There may be absorption there, but without looking at the blood vessels, it's hard to say that for sure," says Sivasankar, who presented her research at the American College of Veterinary Internal Medicine's Forum in June 2004.

In future oral heparin studies, scientists could investigate changes in dogs' blood vessels by examining these tissues after giving oral heparin doses to the animals. "The fact that we didn't see adverse effects in our group of dogs would give researchers the necessary knowledge to pursue this idea further," says Sivasankar.

By examining oral heparin's effects at the level of blood vessels, researchers will gain a much more accurate view of the drug's effects - and finally determine whether oral heparin is a viable option for clinical cases.

Reprinted with permission of Vet Topics, publication for the Western College of Veterinary Medicine's Companion Animal
Health Fund.For more information, visitwww.cahf.usask.ca